Studies are being performed to evaluate the potential immunopathologic significance of host sensitization to cartilage proteoglycan, collagen and chondrocyte antigenic determinants in diverse forms of human destructive arthropathy and in experimental models of inflammatory and degenerative joint disease. The effects of immunologically and non-immunologically derived cytokines secured from diverse cell types and of anti-bodies to constituents inherent to cartilage are to be studied as relates to their potential modulatory capacity upon: a) parameters of normal chondrocyte synthesis and physiologic function and b) proteoglycan aggregation. Experimental models are being developed to study mechanism whereby immunologically and non-immunologically induced activation of enzymes indigenous to chondrocytes may initiate the autocatalytic degradation of cartilage. Further studies are examining the potential pathophysiologic effects of products of deranged chondrocyte synthesis and normal and pathologically derived proteoglycan constituent fractions on normal synoviocyte and chondrocyte metabolic activity and their modulatory potential upon marcrophage, polymorphonuclear cell and lymphocyte afferent and efferent function. Chondrocyte receptor sites are to be studied as are the histologic and biochemical effects on cartilage of systemic administration of cytotoxic agents. Studies are to continue to clarify and extend our findings showing: a) that lymphokines derived by mitogen or cartilage antigen stimulation may through monocyte interaction initiate the degradation of cartilage proteoglycans, b) that lymphokines induced as above manifest a capacity to inhibit chondrocyte proteoglycan synthesis and c) that such lymphokines are able to modulate lysosomal hydrolase mediated cartilage proteoglycan degradation.